The variable character of the HIV-1 epidemicamong world populations suggests that racial distribution of polymorphisms for relevantgenes may be important. Polymorphisms in chemokine receptors have been shown to have aprofound effect on both infection and the rate ofprogression to AIDS in Caucasians. Of thethree protective alleles reported, CCR5-delta32,CCR2-64I, andSDF1-3'A, only CCR2-64I iscommon in African-Americans or native Africans,but it appears to be less protective than inCaucasians. We have identified severalpolymorphisms in HIV-1 candidate genes that occurwith high frequency in African-Americans.Preliminary analyses suggest that there may be complex interactions between chemokine receptorgenes that increase susceptibility to diseaseprogression in a cohort of African Americans. Weare also identifying polymorphisms in bothCaucasians and African-Americans that occur inhost genes encoding proteins, includingtranscriptional factors, that are involved inpost-entry events. Several of these polymorphismsare now being screened for their effects oninfection and progression in the two racial groups.Identification of Candidate Gene Polymorphisms that Influence Progression to AIDS